World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Review Article

Phytopharmacological overview on arjuna Wight and Arn

Narendra Kumar

Amity Institute of Biotechnology, Amity University Haryana, Gurgaon- 122413,

Received: 26-09-2014 / Revised: 13-10-2014 / Accepted: 23-10-2014

ABSTRACT

The application of medicinal to maintain health and treat disease started since time immemorial and still is a part of medical practice.Terminalia arjuna is a tree with simple leaf, smooth and thick bark belonging to the family . Flowers are small, regular, sessile, cup-shaped, polygamous, white, creamy or greenish- white and robustly honey-scented and flowering from April to Julys. Its fruit is a drupe, 2.5–5 cm long, ovoid or oblong, fibrous-woody, smooth-skinned with five hard angles or wings.Ancient Indian physicians used the powdered tree bark of Terminalia arjuna Wight & Arn. for alleviating ―hritshool‖ (angina) and othercardiovascular conditions. Also believed to be a natural liver tonic, Arjuna regulates cholesterol by decreasing LDL levels in the liver. Arjuna is a best hepatitis reliever and heart strengthener for humankind. Leaves of Terminalia arjuna are best healing for hepatitis .Its stem bark possesses glycosides, large quantities of flavonoids, tannins and minerals. Arjuna contains specific active constituents namely Arjunilic acid, Tomentosic acid, Sitossterol, Triterpine glycosides like Arjunetosides , Arjunine and Arjunetein. The bark is rich in Saponnins, natural anti-oxidants (flavonoids-arjunone,arjunolone,leteilin), gallic acid, ellagic acid, phytosterols, rich in minerals like calcium, magnesium, zinc and copper, reducing sugars & coloring matter.The Arjuna bark with its remarkable medicinal properties helps, maintain healthy cholesterol levels. Arjuna is known to possess diuretic properties This have been recorded as antioxidant, anti-inflammatory and lipid lowering effects while glycosides are cardiotonic, thus making Terminalia arjuna unique amongst currently used medicinal plants. In this review an attempt has been made to discuss various aspects of its ethnomedical, phytochemical, pharmacological, antimicrobial, antibacterial, antifungal, insecticidal, antihelmintic, immunomodulatory, antidiabetic, radioprotective, antimutagenic properties for benefit of mankind. Experimental studies have revealed that whole is highly useful staring from its use in cardiovascular tonic to asthma. There is ample evidence of its beneficial effect in coronary artery disease. The extracts of Arjuna are known to help in strengthening the heart muscles, relieving stress, and hypertension. Arjuna is effective for a variety of heart related conditions like high blood pressure, heart palpitations, rapid heartbeat and high cholesterol. These reports are very encouraging and indicate that this should be studied more extensively for its therapeutic benefits.

Key words:Terminalia arjuna, ethnomedicinal, phytochemical, cardiotonic

INTRODUCTION have been described to be beneficial for cardiac ailments in ―Atharva Veda‖ an ancient treatise Terminalia arjuna is a miracle herb which was from which Ayurveda, the Indian system of used during ancient times to cure heart problems. Medicine owes its origin[4,5]. Ancient medical In ancient Ayurvedic literature, Vagbhata and scientists have mentioned the properties of others have described the juice of Arjuna bark as a Terminalia arjuna herb. Indian medical knowledge tonic and astringent. They have recommended it known as Ayurveda goes back millennia. The for the treatment of heart diseases. Arjuna is Vedas and Puranas refer various materials of reported to be a beneficial herb in treating heart medical importance including herbs, plants and problems since 1200 B.C. Vagbhatta was the first trees. In which Terminalia arjuna Wight & Arn. to cite this in his book ‗Astang Hridayam‘ written (arjuna) has prominent place and have been some 1200 years ago [1]. Subsequently, identified and researched for their putative lipid Chakradutta and also Bhawa Mishra, described its lowering and cardioprotective activities [6]. The use in chest pain [2,3]. Several medicinal plants plant which has shown most promising and distinct

*Corresponding Author Address: Dr Narendra Kumar, Senior Lecturer, Amity Institute of Biotechnology, Amity University Haryana, Gurgaon (Manasar-122413), India; E-Mail: [email protected] Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 results is Terminalia arjuna Wight & Arn., pharmacognostical, phytochemical, popularly known as arjuna [7]. Modern research pharmacological, insecticidal, anthelmintic, has discovered that Terminalia arjuna has immunomodulatory, antidiabetic radioprotective antioxidant properties and may be clinically helpful and antioxidant, antimutagenic, toxicity and side in cardiovascular health. A deciduous tree found effects parameters under different conditions. abundantly in the Indian subcontinent, Terminalia arjuna is a heart stimulant that can prove effective SCIENTIFIC CLASSIFICATION: in the treatment of a number of heart conditions. Kingdom:Plantae Found commonly in the Himalayan region, the Division:Magnoliophyta bark of the plant is used by traditional Indian Class:Magnoliopsida medicine for a number of herbal preparations to Order: treat cardiac disorders. Family:Combretaceae :Terminalia Terminalia arjuna is a tree with simple leaf, Species:T. arjuna smooth and thick bark belonging to the family English Name: White Marudah Combretaceae. Flowers are small, regular, sessile, Common (Indian) Names: cup-shaped, polygamous, white, creamy or Hindi: Arjun, Arjuna, Koha, Kahu, Arjan; greenish-white and robustly honey-scented and Gujrati: Arjun - Sadada, Sadado;Canarese: Bili- flowering from April to July. The inflorescences Holo-Nir-Tora Matti, Maddi; Marathi: Arjuna, are short axillary spikes or small terminal panicles Arjun Sadada, Sadura; Sanskrit: Arjuna, Dhanvi, and fruits are obovoid-oblong, dark brown to Indradruma, Kakubha, Karvirak.; Oriya: Arjuna reddish brown fibrous woody, indehiscent drupe Sahajo; and ripening from February to May [8]. All the Tamil: Vellamatta;Telugu: Yerramaddi;Assam: Orj parts of the plant have been used for their un;Bengali: Arjhan;Punjabi: Arjuna therapeutic beneficiary effect from ancient times. T. arjuna helps to maintain a healthy heart and Botanical Details: Terminalia arjuna is a decrease the effects of stress and anxiety [9]. It has deciduous tree found throughout India . The arjuna antibacterial [10], antimutagenic, hypolipidemic, is about 20–25 metres tall; usually has antioxidant and hypocholesterolaemic and anti- a buttressed trunk, and forms a wide canopy at the inflammatory effects. T. arjuna have the capability crown, from which branches drop downwards. It to protect the liver and kidney tissues against CCl4- has oblong, conical leaves which are green on the induced oxidative stress by increasing antioxidative top and brown below; smooth, grey bark; it has defense activities [11]. Its chemical constituents act pale yellow flowers which appear between March as a gastro-protective agent [12]. Different types of and June; its glabrous, 2.5 to 5 cm fibrous woody bioactive compound have been isolated from this fruit, divided into five wings, appears between medicinal plant possesses enormous value in September and November. It has huge, often medicine among then arjunolic acid is very well buttressed trunk and horizontally spreading known. branches. Extent of buttressing in different localities has been found to be due to local factors The aim of the present study was to deliver the and is not determined genetically . Among different literal studies of T. arjuna with its phytochemical species of Terminalia the bark of Terminalia and pharmacological characteristics.Also believed arjuna has its own characteristic features . In a to be a natural liver tonic, Arjuna regulates comparative study of the barks of Terminalia cholesterol by decreasing LDL levels in the liver. It arjuna and Terminalia tomentosa it was found that is advocated by Ayurveda as a liver tonic. The the bark of Terminalia arjuna is smooth, pinkish- extracts of Arjuna are known to help in grey from outside and flakes off in large, curved strengthening the heart muscles, relieving stress, and rather flat pieces. The size of each piece may and hypertension. Arjuna is also thought to fortify vary up to 15 cm or more in length, 10 cm in width the central nervous system and to quicken and 3–10mm in thickness. Sapwood is reddish individual reflexes. Recently there has been white and heartwood is brown and variegated with renewed interest in this plant because of its dark coloured streaks. The histology of Terminalia multimode cardioprotective activity. As there is no arjuna bark reveals the presence of single layered single drug till date which alone or in combination epidermis with hair like projections and few offers definite and reliable protection and/or cure scattered lenticels. Underlying the epidermis is a from the ravages of atherosclerotic cardiovascular thin layer of cortex. Periderm and secondary disorders, the time is ripe for evaluating the role of phloem are present in the old bark . Leaves are Terminalia arjuna in the overall management of simple, borne sub-opposite coriaceous, often related cardiovascular disorders. The present paper crenulating, oblong or elliptic. Their upper face is aims to review its ethnomedical, pale or dark green and the lower face is pale brown.

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 It measures 10–15 cm long and 4–7 cm broad. A Hepatitis/reliever: Arjuna is a best hepatitis network of 10–15 pairs of nerves is arranged in reliever and heart strengthener for humankind. reticulate fashion. Petioles are 6–10mm long with Leaves of Terminalia arjuna are best healing for yellowish or reddish hairs. Linear, lanceolate-like hepatitis C. For heart problems, Arjuna is useful, bracteoles are present. Calyx is glabrous. Its fruit is because important part of glucocide is found in the a drupe, 2.5–5 cm long, ovoid or oblong, fibrous- bark of Arjuna tree. woody, smooth-skinned with five hard angles or wings. The lines of the wings are oblique and In joining of fractured part: Embrocation of curved upwards. arjuna bark powder along with ghee on broken bone can joint again the fractured part. Bark arjuna Distribution and habitat: It is found in abundance after being boiled can be taken as well for throughout Indo-sub-Himalayan tracts of Uttar contacting of bones. Terminalia arjuna is also good Pradesh, South , , Delhi and for reducing swelling of gum and mouth area. Deccan region near ponds and rivers. It is also Gargling with concoction of arjuna barks can heal found in forests of , Burma and skin problems effectively. Tooth bleeding is Mauritius. Terminalia arjuna was introduced in stopped with use of cooked water of arjuna Mauritius by early Indian migrants . Remarkably bark.For blood motion, diarrohoea and dysentery the tree is pest and disease free.The arjuna is arjuna bark is good healer. usually found growing on river banks or near dry river beds in and south and The Cardiotonic Properties of Arjuna: The central India. Terminalia arjuna is a heart stimulant that can prove effective in the treatment of a number of MICROSCOPY: Cork consists of few layers of heart conditions. Found commonly in the tangentially running and radially elongated Himalayan region, the bark of the plant is used by cells;phellogen,2to4 celled thick, phelloderm traditional Indian medicine for a number of herbal narrow, consisting of 4 to 6 rows of tangentially preparations to treat cardiac disorders.As a herb elongated and radially arranged cells, Phloem, very widely supported by Ayurveda, Arjuna has certain broad, traversed by uniserriate medullary rays properties which make it effective for cardiac running straight and parallel occasionally becoming treatment. The tree possesses laghu (light) and slightly curved near the rosette crystal; groups of ruksh (dry) and an abundance of kashaya phloem fibres, lignified, thin-walled, tangentially (astringent) Rasa. The presence of these properties arranged, associated with idioblasts containing make in efficacious for the treatment of Pitta and clusters and rossetes of calcium oxalate. Some Kapha aggravation. The extracts of Arjuna are parenchymatous cells of cortex and secondary known to help in strengthening the heart muscles, phloem contains reddish brown pigment and some relieving stress, and hypertension. Arjuna is cells contain starch grains. effective for a variety of heart related conditions like high blood pressure, heart palpitations, rapid Ethnomedical considerations: The bark leaves heartbeat and high cholesterol. Researches attribute and fruits of Terminalia arjuna have been used in these benefits to certain tannins and glycosides that indigenous system of medicine for different have specific antioxidant properties congenial for ailments [13]. The bark is said to be sweet, acrid, the cardiovascular system. The anti-oxidant cooling and heating, aphrodisiac, expectorant, properties are what make it congenial for tonic, styptic, antidysenteric, purgative and cardiovascular health.Also believed to be a natural laxative. Its use has been advocated in urinary liver tonic, Arjuna regulates cholesterol by discharge, strangury, leucoderma, anaemia, decreasing LDL levels in the liver. It is advocated hyperhidrosis, astringent and diuretic finds mention by Ayurveda as a liver tonic. The extracts of in the works of Carak [14]. The bark powder has Arjuna are known to help in strengthening the heart been attributed to possess cardioprotective muscles, relieving stress, and hypertension. Arjuna properties. Traditional method of its administration is also thought to fortify the central nervous system was to prepare an alcoholic decoction of its bark and to quicken individual reflexes.According to the stem (asava) or give it along with clarified butter Ayurvedic classical description of Terminalia (ghrita) or along with boiled milk arjuna, it is a cooling, Kapha and Pitta pacifying (kshirpak)[15,13]. Having realised the potential herb, helpful in healing wounds, countering obesity atherogenic properties of clarified butter and whole and treating urinary disorders. Ingestion Arjuna milk it would be interesting to examine the role of over a period of time ensures significant cardiac such preparations in experimental model of protection in myocardial infarction commonly atherosclerosis. known as heart attack. The herb is also proven to be helpful in the vasodilatation of blood vessels in

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 chronic smokers and is also known to dissolve arjuna in ischemic mitral regurgitation (IMR) plaque clogging the arteries. following acute myocardial infarction (AMI). 40 patients with fresh AMI showing IMR were According to the Ayurvedic classical description of randomly divided into 2 groups of 20 each. They Terminalia arjuna, it is a cooling, Kapha and Pitta were given placebo or 500 mg of Terminalia pacifying herb, helpful in healing wounds, arjuna in addition to anti-ischemic treatment. After countering obesity and treating urinary disorders.In 1 and 3 months of follow up, patients receiving traditional Indian medicine, Arjuna is adjuvant Terminalia arjuna showed significant recommended as an important cardiotonic plant, decrease in IMR, improvement in E/A ratio and which is known to promote the healthy functioning considerable reduction in anginalfrequency[17] of the heart and in general, acts as a heart tonic. Arjuna extracts help in regulating blood pressure Phytochemical studies: According to World and enhances the healthy functioning of the heart. Health Organization, medicinal plants would be the Arjuna also helps in the reduction of the corrosive best source to obtain variety of drugs [18]. effects of stress and nervousness. Medicinal plants contain some organic compounds which provide definite physiological action on the The Arjuna bark with its remarkable medicinal human body and these bioactive substances include properties helps maintain healthy cholesterol tannins, alkaloids, carbohydrates, terpenoids, levels. Arjuna is known to possess diuretic steroids, flavonoids and phenols. The bio-active properties. It is further corroborated by modern phytocompounds are synthesized by primary or research that Arjuna has antioxidant properties and rather secondary metabolism of living organisms. may be clinically helpful in cardiovascular health. Secondary metabolites are chemically and Studies show that Arjuna is effective for a variety taxonomically extremely diverse compounds with of heart related conditions like high blood pressure, obscure function. They are widely used in the heart palpitations, rapid heartbeat and high human therapy, veterinary, agriculture, scientific cholesterol. Researches attribute these benefits to research and countless other areas. Medicinal certain tannins and glycosides that have specific plants containing active chemical constituents with antioxidant properties congenial for the high antioxidant property play an important role in cardiovascular system. Taken as brewed tea, the prevention of various degenerative diseases powdered, or commercially prepared in capsule [19] and have possible benefits to the humanity. A form, Arjuna has been used in hundreds of large number of phytochemicals belonging to preparations along with other herbs to resolve an several chemical classes have been shown to have incredible number of health issues. In locations inhibitory effects on all types of microorganisms in where the plant is native, Arjuna extracts are used vitro. Botanical medicines or phytomedicines refer to address several health problems.The natural herb to the use of seeds, berries, leaves, bark, root or is believed to regulate cholesterol by decreasing flowers of any plant for medicinal purposes by LDL levels in the liver. It is advocated by significant number of people. Knowledge of the Ayurveda as a liver tonic. The extracts of Arjuna chemical constituents of plants is desirable because are known to help in strengthening the heart such information will be value for synthesis of muscles, relieving stress, and hypertension. Arjuna complex chemical substance [20,21,22]. is also thought to fortify the central nervous system Phytochemical screening showed the active and to quicken individual reflexes. Sinha et al[16] compounds presence in high concentration, such as reported that Terminalia arjuna protects mouse phytosterol, lactones, flavonoids, phenolic hearts against sodium fluoride-induced oxidative compounds and tannins and glycosides. The stress..Fluoride is a ubiquitous environmental antimicrobial activity of extract showed that greater pollutant. They have investigated the antioxidative inhibition zone against Gram negative bacteria than properties of an ethanol extract of the bark of Gram positive bacteria. This methanolic extract Terminalia arjuna against sodium fluoride (NaF)- showed a promising antioxidant activity, as induced oxidative stress in murine heart.The absorption of DPPH redicles decreased in DPPH results suggest that Terminalia arjuna extract free radical scavenging assay. Flavonoids protects murine hearts from sodium fluoride components having antioxidant property present in induced oxidative stress, probably via its the methanol extract at a level of 199.00 mg antioxidant properties. quercetin equivalent/g of dried methanol extract in colorimetric method. The Terminalia arjuna bark In Ischaemicmitral regurgitation: The bark extract revealed the presence of bio-active powder of Terminalia arjuna, an indigenous plant constituents which are known to exhibit medicinal has been found to have antianginal, decongestive as well as physiological activities [23]. In a study and hypolipidemic effect. Dwivedi et al[18] conducted to determine phytochemical planned a study to evaluate the role of Terminalia compositions, chemiluminescence antioxidant

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 activities, and neuroprotective effects on PC12 Tannins: In addition to flavonoids variety of cells for water, methanol, and 95% ethanol extracts tannins have been isolated from the bark of of the air-dried fruit of Terminalia. the water Terminalia arjuna. Some of the wellknown extract afforded the greatest yield, and total hydrolysable tannins from the bark are phenolic and tannin content. The methanol extract pyrocatechols, punicallin, punicalagin, terchebulin, yielded the greatest total triterpenoid content. terflavin C, castalagin, casuariin and casuarinin. Based on four chemiluminescence antioxidant Some 15 types of tannins and related type of assays, the three extracts showed various degrees compounds have been isolated from its bark so far of antioxidant activity. The methanol extract [26]. Tannins are known to enhance synthesis of showed good antioxidant activity based on the nitric oxide and relax vascular segments horseradish peroxidase-luminol-hydrogen peroxide precontracted with norepinephrine. It may well be (H2O2) assay. The water extract appeared to have that tannins may be contributing to the reported good antioxidant activities in cupric sulfate-Phen- hypotensive action of Terminalia arjuna bark [27]. Vc-H2O2 and luminol-H2O2assays. Pyrogallol- It is also speculated that tannins may be luminol assay showed the 95% ethanol extract to responsible for its astringent, wound healing and have good antioxidant activity. The methanol and anti microbial activity [27]. water extracts presented neuroprotective activities on H2O2-induced PC12 cell death at 0.5–5.0 μg/mL Minerals: The bark also contains large amounts of [25].Arjuna contains specific active constituents magnesium (4000_g/g), calcium (3133_g/g), zinc namely Arjunilic acid, Tomentosic acid, (119_g/g), copper (19_g/g) and silica [7]. Sitossterol, Triterpine glycosides like Arjunetosides I, II, III, IV, Arjunine and Arjunetein. The bark is Antimicrobial activity: Ear infection is one of the rich in Saponnins, natural anti-oxidants common diseases occurring throughout the world. (flavonoids-arjunone,arjunolone,leteilin), gallic Different etiological agents are responsible for ear acid, ellagic acid, phytosterols, rich in minerals infections.To assess the antimicrobial potential of like calcium, magnesium, zinc and copper, Terminalia arjuna leaves and bark extracts against reducing sugars & coloring matter. Staphylococcus aureus, Acinetobacter sp., Proteus For phytochemical screening, some common and mirabilis, Escherchia coli, Pseudomonas available standard tests were done. Antimicrobial aeruginosa and Candida albicans, pathogens bioassay was done through agar well diffusion causing ear infections and their comparison with method. Detection of antioxidant activity and locally available ear drops were studied.Methanol, flavonoid compounds were done through thin layer ethanol, acetone, aqueous (hot and cold) extracts chromatography. Total antioxidant activity was from the leaves and bark of T. arjuna were tested measured by 2, 2-diphenyl-1-picrylhydrazyl for their antimicrobial activity.Of the three organic (DPPH) in colorimetric method. Aluminum solvents evaluated, acetonic leaf extract was found chloride colorimetric method was used for total to be best against S. aureus. Organic bark extract flavonoid determination. Phytochemical screening showed almost equal inhibition of all tested Gram showed the active compounds presence in high negative bacteria except P. aeruginosa. However, concentration, such as phytosterol, lactones, aqueous extract of T. arjuna bark exhibited good flavonoids, phenolic compounds and tannins and activity against S. aureus.Organic extract obtained glycosides. The antimicrobial activity of extract from the T. arjuna bark and leaves may be used to showed that greater inhibition zone against Gram treat the bacterial ear pathogens especially S. negative bacteria than Gram positive bacteria. This aureus, which has shown greater inhibition zones methanolic extract showed a promising antioxidant than the herbal drops[28]. activity, as absorption of DPPH redicles decreased in DPPH free radical scavenging assay. Flavonoids Anti-bacterial Activity: Morbidity and mortality components having antioxidant property present in due to diarrhoea continues to be a major problem in the methanol extract at a level of 199.00 mg many developing countries. Water samples from quercetin equivalent/g of dried methanol extract in different areas of Chittagong were collected and 22 colorimetric method. The Terminalia arjuna bark Vibrio cholerae were isolated from the samples. In extract revealed the presence of bio-active this experiment we found that 85% of the Vibrio constituents which are known to exhibit medicinal cholerae isolated can grow at 6% NaCl whereas as well as physiological activities [24]. Mythill et none of these can survive at 8% NaCl. Most of the al [25] reported that Terminalia arjuna isolates were resistant to at least 2 antibiotics. triterpenoids extract containing arjunolic acid has 95.45% were resistant to ampicillin, 50% to protective effect against cyclosporine induced erythromycin, 63.63% to nalidixic acid, 13.63% to cardiotoxicity. cephotaxine, 13.63% to ceftriaxone and 27.27% to cotrimoxazol. Arjun bark extract was used as a biological tool to resolve the antibiotic resistant V.

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 cholerae problem. Arjun extract inhibited the Terminalia arjuna, Erythrine caffra, Taxodium growth of V. cholerae at all concentrations and distichum and Melaleuca cajuputi. Treatment with zone diameter increased with the increase of each of the four plant extracts caused clear concentrations. The regression coefficient of the mortality on 4th instar larvae. The reduction in F1 relationship between concentration and zone progeny , elongation of the larval duration, and diameter varies from 0.75 to 0.984 for most of the pupal period at any of the tested concentration were isolates which indicates that there exists a linear noticed . There was moderate gradient reduction in relationship. This revealed that Terminalia arjuna the pupation percentage of the different treatments would be a good antibacterial drug in the treatment (71) as compared to the control (93.3). Moderate of Vibrio cholerae infections, provided if found fluctuation was observed among sex ratio (1:2.3). effective and nontoxic through in vivo Percentages of adult emergence and growth were studies[29].Morsheed et al[30] evaluated the inhibited with increasing the concentrations as antibacterial and cytotoxic activity of 50% ethanol observed in four plant extracts (1.7) as compared to extract of bark from Terminalia arjuna on selected control (2.9). four Gram positive and eight Gram negative bacterial strains. The bark extract of Terminalia Anthelmintic activity: The study was carried out arjuna showed potential antimicrobial activities to evaluate the anthelmintic activity of Terminalia against all of the selected strains of microorganisms arjuna (Roxb.) bark locally used as an and the greatest activity was observed against anthelmintic. Lethal median concentration (LC50 Shigella dysenteriae. For antimicrobial test, Disc values) of methanolic extract of T. arjuna bark in diffusion technique was used and the zone of egg hatch and larval development tests against inhibition of microorganisms was measured in mm. Haemonchus contortus ova and larva were found to In vitro cytotoxicity test was also studied by Brine be 645.65 and 467.74 µg mL-1, respectively. In Shrimp Lethality Bioassay and results illustrated adult motility assay, efficacy of the extract was significant (p<0.05) cytotoxicity against A. salina, evident by the mortality of H. contortus at different that were expressed as LC50. Terminalia arjuna hours post exposure. In vivo results revealed ethanol extract showed brine shrimp cytotoxicity maximum (87.3%) egg count percent reduction with lethal concentration 50 (LC50) value of 50.11 (ECR) in sheep treated with crude methanolic μg/ml. To observe antibacterial activity four extract @ 3 g kg-1 body weight on day 11 post- Gram-negative and two Gram-positive bacteria treatment (PT). The data revealed dose-dependent were tested using agar well diffusion method. The anthelmintic activity both in the in vitro and in vivo results indicate that antibacterial activity of the studies, thus justifying its use in the traditional extract were concentration dependent ranging from medicine [34]. 0.5-10mg/ml. The striking and distinctive feature of observed antibacterial activity of T. arjuna Immunomodulatory Efficacy: A study was extract is that it exhibited decent activity against made for the evaluation of the immunomodulatory the multi-drug resistant Gram- negative bacteria efficacy of Terminalia arjuna bark extract in Coliform spp, Klebsiella pneumoniae, Aspiculuris tetraptera infected mice. The plant Pseudomonas aeruginosa even at low extract were administrated to the infectedmice on concentrations( 3mg/ml).Minimum Inhibitory 18 , 19 and 20 post infection days. The Concentration(MIC) was predicted for the extract immunomodulatory efficacy due to plant extract and it was varied from 3-20mg/ml[31]. was observed th th th on ITH, DTH and Lymphocyte response. PCA, DTH and Antifungal activity: Aqueous, alcoholic and ethyl Lymphocyte response reactions were found to be acetate extracts of leaves of five Terminalia species directly proportional to the dose of drug. PCA (T. alata, T. arjuna, T. bellerica, T. catappa, T. response was maximum (8.2 mm) in the group chebula) were tested against five plant pathogenic ITTAM and 5 minimum (5.8 mm) in the group fungi like Aspergillus flavus, Aspergillus niger, ITTAA . DTH response was maximum (7.8 mm) in Alternaria brassicicola, Alternaria alternata and the group ITTAM and 1 5 minimum (4.9 mm) in Helminthosporium tetramera). The antifungal the group ITTAA .Lymphocyte count was observed activities of all these extracts were determined by maximum (79%) in the group ITTAM 1 5 and paper disc method. Nearly all the extracts were minimum (68.6%) in the group ITTAA . found effective against these fungi. It was found Significant increase in PCA, DTH and lymphocyte that most of[32]. responses in 1 the infected and treated mice indicates stimulated cell mediated as well as Insecticidal Activity: Hazaa et al [33] investigated humoral immunity. Obtained results indicate that the toxic effect of some plant extracts on cotton studied plant extract can be good leaf worm, Spodoptera littoralis (Boisd.). immunnomodulatory agent and may boost the Petroleum ether extract of some planta such as immune response of the host but. We conclude that

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 methanol extract of Terminalia arjuna is more single dose of streptozotocin (STZ; 40 mg/kg, effective than aqueous extract of Terminalia arjuna intraperitoneally). Control and diabetic rats were plant[35]. treated with TA (500 mg/kg) for four weeks. After TA treatment, blood was drawn and rats were then Antidiabetic effect: The study was carried out to sacrificed, and their liver and pancreas were evaluate the antidiabetic effect of T.arjuna dissected out for biochemical assays. The level of stembark extract and to study the activities of fasting blood glucose (FBG), glycated hemoglobin hexokinase, aldolase and phosphoglucoisomerase, (HbA1C), total cholesterol (TC), triglycerides and gluconeogenic enzymes such as glucose-6- (TG), low density lipoprotein-cholesterol (LDL-C) phosphatase and fructose -1,6-diphosphatase in and very low density lipoprotein-cholesterol liver and kidney of normal and alloxan induced (VLDL-C) significantly (P < 0.05) increased while diabetic rats. Oral administration of ethanolic high density lipoprotein cholesterol (HDL-C) and extract of bark (250 and 500mg/kg body weight) hepatic glycogen decreased in the HFD/STZ group. for 30 days, resulted in significant decrease of TA treatment augmented these effects in the blood glucose from 302.67 ± 22.35 to 82.50 ± HFD/STZ + TA group. The HFD/STZ group 04.72 and in a decrease in the activities of glucose- showed elevated renal injury markers in serum, 6-phosphatase, fructose-1,6-disphosphatase, including blood urea nitrogen (BUN), serum aldolase and an increase in the activity of creatinine (Scr) and alkaline phosphatase (ALP), phosphoglucoisomerase and hexokinase in tissues. which were decreased significantly (P < 0.05) by However, in the case of 250 mg / kg body weight TA treatment. Moreover, treatment with TA of extract, less activity was observed. The study significantly (P < 0.05) ameliorated thiobarbituric clearly shows that the bark extract of T.arjuna reactive substances (TBARS), malonaldehyde possesses ppotent antidiabetic activity[36]. Barman (MDA) and protein carbonyl (PC), and glutathione and Das[37] reported the effect of ethanolic (GSH), glutathione-s-transferase (GST) and extract of bark of Terminalia arjuna on blood catalase (CAT) in liver and pancreas of HFD/STZ glucose level of normal and diabetic rats. Healthy group. The study suggests that TA is effective in Wistar albino rats (100-150 gm) were divided into reducing hyperglycemia, hyperlipidemia and four groups of six animals each. Normal control oxidative stress related to the risk of diabetes. group received normal saline (10 ml/kg/day/p.o.); Thus, it may have a therapeutic value for the diabetic treated group received ethanolic extract of treatment of T2DM[38]. bark of Terminalia arjuna (500 mg/kg/p.o.); diabetic standard group received Glibenclamide Radiaprotective and antioxidant properties: (0.5 mg/kg/day/p.o.) given for 2 weeks. To induce Using rat liver mitochondria as model systems, the diabetes, alloxan 150 mg/kg, i.p. single dose was radioprotective and antioxidant effects of the Indian administered to diabetic control, diabetic treated medicinal plant Terminalia arjuna was examined. and diabetic standard groups. Blood glucose and Various sohxlet fractions of the bark and the body weight was estimated weekly for two weeks. medicinal formulation arjunsal besides an active For mechanism of action glycogen estimation on ingredient, baicalein, were examined for their liver, cardiac and skeletal muscle; effect on ability to protect both rat liver mitochondria and adrenaline induced hyperglycemia and intestinal cardiac homogenate against radiation and oxidative glucose absorption was done. For hypoglycemic stress apart from their ability to scavenge radicals action on normal rats, blood glucose was estimated and for ferric reducing/antioxidant power. Among at '0' min and '120' min. The drug showed the various extracts from arjunsal the ones from significant decrease ( P<0.01) in blood glucose organic solvents were found to be the most level. The test drug showed a significant ( P<0.01) effective in DPPH, ABTS and FRAP assays. In T. increase in glycogen content in liver, cardiac and arjuna bark, the methanolic extract showed the skeletal muscle, significantly ( P<0.01) reduced highest antioxidant activity. Radioprotection adrenaline induced hyperglycemia and intestinal studies also showed that the methanolic extract was glucose absorption. Blood glucose in normal rats the most effective. Baicalein showed antioxidant as was significantly ( P<0.01) decreased in drug well as radioprotective activity. To look at the treated groups. This revealed that Terminalia possible mechanisms for the observed arjuna bark possesses significant hypoglycaemic antioxidant/radioprotective effects pulse radiolysis and anti-diabetic activity. A study was designd to was performed to examine the reactions of evaluate the beneficial effects of Terminalia arjuna baicalein with various radiation-related and (TA) extract on hyperglycemia, lipid profile, renal biologically relevant reactive species such as damage markers and oxidative stress in the liver hydroxyl radical (•OH), azide radical (N3• ), lipid and pancreas of type 2 diabetes mellitus (T2DM) in peroxyl radical (LOO• ), trichloro methyl operoxyl rats. T2DM was induced by feeding rats with high- radical (CCl3O2• ) and thiyl (RS• ) radical. fat diet (HFD; 40%) for two weeks followed by Baicalein reacts with these radicals at almost

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 diffusion controlled rates. The bimolecular rate antinococeptive action probably mediated via constants for the reaction of these radicals were in central opioid receptors.[42]. the order of 109 dm3mol-1s-1. The above results indicate that various preparations from T. arjuna Micropropagation: Cotyledonary node explants and its component baicalein have significant excised from 21 day old seedlings of T. arjuna radioprotective and antioxidant activities and the produced multiple shoots when cultured on full ability to react with radiation-derived or radiation- strength MS or modified MS (1/2 strength major related reactive species may be the factor salts and Fe-EDTA) medium supplemented with responsible [39]. Sivalokanathan et al [40] different concentrations (0.1-1.0 mg/l) of BAP. investigated to evaluate the antioxidant nature of Maximum 8.9 shoots/explant could be recorded ethanolic extract of Terminalia arjuna bark on N- after 30 days of inoculation on modified MS nitrosodiethylamine (DEN) induced liver cancer in medium supplemented with BAP (0.5 mg/l). A male Wistar albino rats. The results show an proliferating shoot culture was established by antioxidant activity of Terminalia arjuna bark reculturing the original cotyledonary nodes (2-3 against DEN-induced liver cancer times) on shoot multiplication medium after each harvest of the newly formed shoots. Shoots (each Antimutagenic activities: The antimutagenic having 2-3 nodes/shoot) thus obtained were also effect of benzene, chloroform, acetone and used as a source of nodal explant that gave rise to methanol fractions from Terminalia arjuna was 1-2 shoots when cultured on modified MS+BAP determined against Acid Black dye, 2- (0.5 mg/l) medium. Thus, 45-55 shoots could be aminofluorene (2AF) and 4-nitro-o- obtained after 60 days of culture initiation from a phenylenediamine (NPD) in TA98 Frameshift single cotyledonary node. About 88% shoots rooted mutagen tester strain of Salmonella typhimurium. well after 15 hr pulse treatment with IBA (1 mg/l) Among the different fractions, the antimutagenic in liquid MS medium followed by transfer to effect of acetone and methanol fractions was more modified MS medium without IBA. About 80% of than that observed with other fractions. Co- these plantlets were successfully acclimatized in incubation and pre-incubation modes of plastic pots containing sand and soil mixture and experimentation did not show much difference in 70% plantlets transferred in the field those survived the antimutagenic activity of the extracts. even after 6 months of transplantation[43]. Moreover, these fractions inhibited the S9- dependent mutagens, 2AF and Acid Black dye In acne management more effectively than the direct-acting mutagens. Prepare an ointment by mixing finely powdered bar Studies are under way to isolate and elucidate the k with honey and apply it over acne eruptions. It is nature of the antimutagenic factor in acetone and said to be a successful treatment in acne. methanol fractions[41]. Aphrodisiac Properties If powder of bark is taken, regularly with milk for 2 Anti-inflammatory, immunomodulatory and 3 months or till improvement sets in, it will prove a antinociceptive activity: Terminalia arjuna back s an effective sex stimulant. powder (400 mg/kg, po) significantly reduced formalin-indued paw oedema at 24 h but not In asthma management: carrageenan-induced paw oedema. It significantly The treatment should be carried on the night of full increased the anti-SRBC antibody titre in the moon. Prepare a dish from condensed milk sugar a secondary phase of immune response. The same nd rice to make a palatable kheer and put in an ope dose significantly reduced the duration of licks and n bowl which should be covered with a thin muslin bites in both phases of formalin-induced pain clothand exposed to moonlight, making sure that th response and showed significant increase in tail e moonlight falls directly on the processed dish. flick latency at higher dose (800 mg/kg, po). These Sprinkle10- effects of T. arjuna were antagonised by 12 gms of powder of the arjuna bark over it and eat pretreatment with naloxone (1 mg/kg, ip). In early next morning, but the patient must not sleep another series of experiments, mice pretreated with upto twelve hours afterconsuming the dish. This is morphine for three days in increasing doses (10, said to be an effective and curative device in case o 15, 20 mg/kg, ip; twice daily) showed a decreased f even chronic asthma [44]. response in antinociceptive activity of morphine (5 mg/kg, ip). Further, cross tolerance was observed Modern research and Arjuna: Modern clinicians with T. arjuna (800 mg/kg, po) in morphine are just beginning to use arjuna for coronary artery tolerant animals. These findings support the disease, heart failure, and high cholesterol. The hypothesis that T. arjuna has anti-inflammatory herb‘s components include a variety of potential against some phlogistic agents along with polyphenols, which probably account for much of some immunomodulatory activity and also has its activity. They include three flavonoids

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 (arjunone, arjunolone, and luteolin), four mild gastritis, headache and constipation. No triterpenoid saponins (arjunic acid, arjunolic acid, haematological, metabolic, renal and hepatic arjungenin, and arjunglycosides), tannins, ellagic toxicity has been reported even more than 24 acid, gallic acid, and proanthocyanidinic oligomers. months of its administration[45,46,47]. There have Arjuna also contains phyto-sterols, calcium, been few reports which have shown its hepato- magnesium, zinc, and copper. Arjuna seems to renal protective property. In a recent study the work by improving cardiac muscle function and the aqueousextract of its bark could protect the liver pumping activity of the heart. The saponin and kidney tissues of mice against carbon tetra glycosides might be accountable for this effect, chloride (CCl4)-induced oxidative stress probably while the flavonoids and proanthocyanidinic by increasing antioxidant defence activities[48]. In oligomers contribute antioxidant action and another study using ethanolic extract, 500 mg/kg strengthen veins. Scientific information about dose of its bark stem in alloxan-induced diabetic arjuna is beginning to accumulate. Angina pectoris rats, it was found that the drug reduced the lipid patients in particular may benefit from arjuna. A peroxidation and raised endogenous antioxidant 1999 study indicated that arjuna was more effective enzymes in liver and kidney tissues . than a standard drug for angina. Arjuna was effective for 80 percent of the patients, and the herb Conclusions and future strategies: The herbal reduced the number of angina attacks from remedies have been employed in varius medical seventy-nine per week to twenty-four per week. In system for the treatment and management of a recent study from India, patients with stable different diseases.The plant Terminalia arjuna has angina cut their heart pain in half after three been used in different system of traditional months of therapy with arjuna alone. When the medication for the treatment of diseases and researchers examined the patients‘ overall clinical ailments of humam beings.The plant contains condition, treadmill results, and heart strength, 66 arjunilic acid,triterpinne glycosides,natural percent showed improvement. Arjuna is oxidants,gallic acid,phytosterols,rich in minerals particularly effective for congestive heart failure. A like Ca,Mg,Zn and Co and reducing sugar and recent experiment bears this out. A double-blind, colouring matter.It has been reported as placebo-controlled, two-phase trial of arjuna extract cardiotonic, hepatoprotective, immunomodulatory, in patients with severe cases of the condition was antimicrobial, insecticidal, anthelmintic, conducted. Arjuna was added to the patients‘ antidiabetic, radioprotective, antioxidant, regular drugs. In just two weeks, breathing antimutagenic properties. The efficacy of difficulties, fatigue, edema, heart contraction, blood Terminalia arjuna is much popular as an anti- pressure, and walking tolerance all improved. In ischemic agent and as a potent antioxidant . It can the second phase of the study, the subjects be considered as a useful drug for coronary artery continued taking the arjuna for two years. Their disease, hypertension and ischemic conditions continued to improve for the first two to cardiomyopathy. Its actions in different cells of the three months of the study‘s second phase, and the cardiovascular system need much attention. improvements were maintained during the entire Further, a well-designed study to evaluate its two years. Arjuna also benefits cardiomyopathy, or toxicity from its long-term use is another priority. weakening of the lower muscles of the heart, and Such a study will provide scientific basis for its may help patients recovering from heart attacks. A clinical use .As the global scenario is now changing 1997 study of heart attack victims demonstrated towards the use of non toxic plant products, that arjuna was superior to drugs alone for a wide development of modern drugs should be range of related symptoms, including angina, emphasized. Clinical trials should be conducted to enlargement of the heart, and impaired pumping support its therapeutic value.The current study is strength. therefore carried out to provide requsite phytochemical and pharmacological detail about Additional actions of Terminalia arjuna herb: the plant.The plant is cultivated in different parts of Terminalia arjuna has compounds that protect India on a small scale.However systematic against DNA damage from toxins. Compounds in information on different aspects of this species is arjuna may help maintain healthy cholesterol. still not available.In this review an attempt has A substance in arjuna, casuarinas, inhibits breast been made to present this information. cancer cell growth. ACKNOWLEDGEMENTS Toxicity and side effects: Terminalia arjuna has The valuable suggestions rendered by Prof. been used in the dose of 1–2 g/day in various S.M.Paul Khurana,Director Amity Institute of clinical studies. This has been found to be the Biotechnology for the preparation of manuscript optimum dose in patients of CAD. At this dosage, and providing Laboratory and Library facilities is it is well tolerated and has fewer side effects like highly acknowledged.

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Kumar, World J Pharm Sci 2014; 2(11): 1557-1566 REFERENCES

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